Risk assessment methods evaluate of a body of evidence to determine the potential for adverse outcomes; however, assessment of endocrine disruption potential requires an extension of the standard paradigm to assess biological pathways, or mechanisms of action. Evidence-based methods, including systematic review, scoping reviews, and systematic generation of evidence inventories facilitate rigorous and transparent assessments of endocrine activity when combined with existing knowledge about estrogen (E), androgen (A), thyroid (T), and steroidogenesis (S) modalities. Collectively, they provide a structured biological platform to organize and integrate evidence in pathwaybased assessments. Using case studies of chemicals from consumer products and environmental contaminants, the presentation will demonstrate the challenges and the utilities of applying evidence-based methods in the evaluation of potential endocrine disruption properties. In one example, the ECHA/EFSA guidance was applied to a large and heterogenous evidence base which includes >80 studies of varying design: epidemiological, in vivo and in vitro guideline-based assays, nonguideline in vivo and assays, and high-throughput datasets. Using a structure approach, each experimental dataset was extracted to capture EATS modalities and the weight of evidence was determined for the potential for activity and adversity based on the level (1–5) of the assays, study quality, along with direction of activity, consistency, magnitude. These data were subsequently integrated using a structured approach to assess endocrine-mediated modes of action (hazard), characterize uncertainty, and finally in the development of risk-based conclusions